23 results about "Rituximab" patented technology

Purinostat mesylate (PM) for preventing and treating diffuse large B-cell lymphoma (DLBCL), an analogue thereof, a drug for combined use, and the use. PM exhibits excellent in-vivo and in-vitro anti-tumor therapeutic effects on DLBCL (DEL and DHL) subtypes with poor prognosis, DLBCL subtypes having TP53 deletion and mutation combined with a plurality of poor prognosis gene mutations, and DLBCL having TP53 mutation with double expressors, which are superior to that of most existing DLBCL clinical therapy plans. A doublet or triplet therapy of PM with rituximab, R-CHOP, venetoclax and R-CHP also exhibits excellent in-vivo therapeutic effects against DLBCL and a plurality of subtypes. Thus, PM and the drug for combined use have an important clinical significance for the DLBCL and a plurality of subtypes.

The invention discloses an Au (at) Pt nano-enzyme probe as well as application and a kit thereof. The Au (at) Pt nano enzyme probe is composed of Au (at) Pt nano enzyme and a CD20 antibody; the CD20 antibody is modified on the surface of the Au (at) Pt nano-enzyme. According to the preparation method disclosed by the invention, the Au (at) Pt nano-enzyme with a core-shell structure and a hydrodynamic size stabilized at 25nm is synthesized through specific steps, and the Au (at) Pt nano-enzyme probe modified by the CD20 monoclonal antibody (Rituximab) is prepared, so that the traditional two-step immunohistochemical detection is replaced. A proper DAB buffer solution and a proper reaction solution are prepared, so that clear and accurate chromogenic reaction is initiated, and a solid guarantee is provided for the reliability of an immunohistochemical staining result. Compared with the prior art, the immunohistochemical process is simplified, the cost is reduced, the detection efficiency and accuracy are improved, and an efficient and reliable scheme is provided for clinical diagnosis and scientific research.

The invention discloses a flexible conformal litexitinib drug delivery microneedle and a preparation method of the flexible conformal litexitinib drug delivery microneedle. The microneedle comprises a medicine carrying layer, a flexible substrate and a packaging layer. Wherein the medicine carrying layer is composed of biological-friendly hydrogel and litexitinib, the flexible substrate is photo-crosslinked polyethylene glycol diacrylate composite hydrogel, and the packaging layer is made of an elastic chemical-resistant high polymer material. The preparation method of the microneedle comprises the steps of preparation of drug-loaded hydrogel, preparation of a flexible substrate precursor, pouring of the drug-loaded layer, bonding of the light-cured flexible substrate, packaging and the like. Particularly, the microneedle has adjustable geometric parameters, good mechanical strength and excellent drug loading capacity, and transdermal drug delivery can be realized; the flexible substrate layer has viscidity and can be bonded with the medicine carrying layer and the packaging layer, and therefore the medicine delivery microneedle highly conformal to the focus position is constructed. The dosage form and the structure of the drug delivery microneedle are optimized, and efficient drug delivery of focuses such as targeted skin is achieved.

Therapeutic combinations of an AKT inhibitor, a BCL-2 inhibitor and an anti-CD20 antibody are described. Preferably, the combination comprises capivasertib, venetoclax and rituximab. The combinations can be useful in the treatment of B-cell malignancies.

The invention discloses a method for evaluating the drug effect of rituximab on primary membranous nephropathy. According to the method, an SNP (Single Nucleotide Polymorphism) site rs396991 of FCGR3A is mutated into AC or CC from wild type AA, and the 158th amino acid coded by the SNP site rs396991 is mutated into phenylalanine from valine; according to the invention, an iMLDR typing technology is adopted to detect an FGCR3A base mutation site, if rs396991 is AA type, the rs396991 is considered to be effective to an RTX drug, and if the rs396991 is detected to be AC type or CC type, the rs396991 is considered to be insensitive or ineffective to an RTX reaction; therefore, the rituximab can be used for effectively evaluating the drug effect of the rituximab on the primary membranous nephropathy.

To provide polynucleotides encoding chimeric antigen receptors (CARs) comprising a CD19 antigen binding domain that specifically binds to CD19 and is resistant to rituximab binding, and immune cells comprising these CD19-specific CARs, e.g., CAR-T cells.SOLUTION: An isolated polynucleotide encoding a polypeptide including an anti-CD19 chimeric antigen receptor (CAR) that is at least 70% identical to SEQ ID NO: 9, wherein the polypeptide does not include a rituximab binding site, and the polynucleotide includes a short EF1a promoter that is capable of expressing the anti-CD19 chimeric antigen receptor (CAR) in a mammalian T cell.SELECTED DRAWING: None

The invention discloses an antigen expression vector, a combination of the antigen expression vector and an antibody and application of the combination in cancer treatment. The antigen expression vector comprises one or more DMP-antigen coding gene units; the DMP-antigen coding gene is composed of two functional elements DMP and an antigen coding gene, the DMP is an NF-kappa B specific promoter, and the antigen coding gene is an antigen molecule coding sequence. The antigen expression vector prepared by the invention can selectively express antigen molecules in cancer cells, an in-vivo delivery vector taking adeno-associated virus as the antigen expression vector, and a combination of an antigen CD20 expressed by the antigen expression vector and an anti-CD20 antibody rituximab. The compound has a good treatment effect on mouse colon cancer on mice and human colon cancer on humanized mice, and has good tumor targeting property and safety in the treatment of the cancer mice. The invention is expected to provide a new technology and a new reagent for the treatment of various cancer diseases.

This disclosure includes methods for treating cancer in a subject, the method comprising administering an anti-CD20 antibody and an immune cell expressing a therapeutic polypeptide (e.g., a TEAM) to the subject.

Introduction: Rituximab (R) is an integral component of therapy for B-cell lymphoid malignancies; bortezomib (Btz) has shown provocative single agent activity in Follicular Lymphoma (FL), Mantle Cell Lymphoma (MCL) and Waldenstrom's Macroglobulinaemia (WM), providing the rationale for investigating the combination.Patients+Methods: Forty-five adult patients (pts.) (30 men, 15 women) with histologically confirmed recurrent CD20+ve FL, MCL or WM, median age 60 years (range 45-79), FL: 17, MCL: 18, WM: 10, stage III / IV 40 (93%), bone marrow (BM) infiltration 32 (73%), elevated LDH 22 (49%), performance status ≥1 22 (49%), were enrolled in a randomised trial comparing 2 schedules of Brz+R: Arm A (twice weekly) Btz: 1.3 mg / m2 (on days 1, 4, 8, 11 of a 21-day cycle) and R: 375 mg / m2 (on day 1) for 8 cycles, or Arm B (weekly) Btz: 1.6 mg / m2 (on days 1, 8, 15, 22 of a 35-day cycle) and R: 375 mg / m2 (on days 1, 8, 15, 22 of cycles 1 and 4) for 6 cycles (23 arm A, 22 arm B). The median number of previous treatments was 2 (range 1-7). Seventeen pts. had received a R-containing regimen, with response lasting >6 months, and 8 high-dose treatment. Response was evaluated using the IWR criteria (Cheson et al, JCO 17:1244, 1999) and the updated response criteria from the 3rd International Workshop on WM (Treon et al, Blood 107:3442, 2006)Results: Ability to deliver the therapy, toxicity and efficacy were equivalent in both arms. The median number of cycles given in arm A was 4 and 5 in arm B. Haematological toxicity (grade≥3: anaemia 0%, neutropenia 25%, thrombocytopenia 22%) was significantly influenced by the high percentage of pts. with BM infiltration and concomitant cytopenia on entry to the trial. The most common non-haematological adverse events were fatigue (76%), nausea (56%), diarrhoea (56%), lethargy (46%). Neurotoxicity occurred in 19 pts. (46%) (10 pts. grade 1, 7 pts. grade 2, 2 pts. grade 3). Btz dose was reduced in 7 pts.; 5 doses were omitted because of neuro or haematological toxicity. In 16 pts., treatment was delayed by 1-14 days and in 24 pts. treatment was stopped prematurely. The reasons for stopping treatment were: treatment-related toxicity 11 pts., progressive disease 9 pts., patient's preference 3 pts., myocardial infarction 1 pt. One pt. was excluded having been found ineligible post randomisation. Thirty-nine pts. (21 arm A, 18 arm B) are evaluable for response so far, one having only received 1 cycle of therapy, which had to be discontinued because of excessive toxicity. 15 / 32 were in remission (CR, CRu, PR) at the completion of therapy, 7 / 7 at “mid-therapy” assessment, and 5 have yet to be evaluated. Thus the overall response rate (RR) presently is 22 / 39 (56%) (CR, CRu, PR), FL 44%, MCL 46%, WM 90%.Conclusions:The combination was active in pts. with recurrent NHL especially WM (RR 90%), despite multiple previous treatments, The weekly schedule is preferable being more convenient, as efficacious and no more toxic.Further investigation is warranted, despite not insignificant therapy compromising toxicity.

Provided herein are polynucleotides encoding chimeric antigen receptors (CARs) comprising CD19 antigen-binding domains that specifically bind to CD19 and are resistant to rituximab binding; and immune cells, such as CAR-T cells, comprising these CD19-specific CARs. The present invention also provides methods for manufacturing and using these CD19-specific CARs, and immune cells comprising these CD19-specific CARs.

The invention provides targeted precise immunotherapy by applying a biological protein nano-robot to carry a biological agent and a preparation method of the biological protein nano-robot, and relates to the field of immunotherapy, the preparation method comprises the following steps: S100, preparing a serum albumin aqueous solution with the serum albumin concentration of 5-10% w / v, and a phosphate buffer solution with the pH value of 7.4 as a solvent; and S200, preparing an organic solution of a hydrophobic anti-rheumatism drug, wherein the drug is one or more of adalimumab, jucuiliumab, ezetizumab, tetronigerb, tolzumab and rituximab. When the albumin nano-robot targeting drug is used for treating rheumatism, effective targeting can be realized by utilizing the chemotactic effect of the albumin nano-robot targeting drug for immunotherapy on high-expression iNOS and ROS in an immune microenvironment, and the released anti-rheumatism drug and nitric oxide play a synergistic effect for combined treatment; wherein the anti-rheumatism medicine and nitric oxide (NO) generated in the targeting process of the nano-robot can jointly start immune circulation in vivo, and the anti-rheumatism medicine and the nitric oxide (NO) cooperate with the chemotherapy medicine to achieve the killing effect, so that the combined treatment effect is achieved.

Provided herein are polynucleotides encoding chimeric antigen receptors (CARs) comprising a CD19 antigen binding domain that specifically binds to CD19 and is resistant to rituximab binding; and immune cells comprising these CD19-specific CARs, e.g., CAR-T cells. Also provided are methods of making and using these CD19-specific CARs, and immune cells comprising these CD19-specific CARs.

This document relates to methods and materials involved in identifying and / or treating mammals having membranous nephropathy (e.g., membranous nephropathy with an elevated level of a Semaphorin 3B polypeptide in the glomerular basement membrane (GBM)). For example, methods and materials for administering one or more immunosuppressive agents (e.g., corticosteroids, cyclosporine, or a B-cell reduction or depletion agent such as Rituximab) to treat a mammal (e.g., a human) having membranous nephropathy are provided.

Provided herein are novel anti-CD20 antibodies that exhibit several advantageous properties as compared to rituximab.

This invention relates to a preparation process of litexitinib tosylate. In the preparation process described in this invention, the raw material undergoes an amidation reaction of a carbonyl group and an amino group. After the amide is reduced, it is resolved by L-DBTA to obtain the desired chiral compound, and finally, it is salted with p-methanesulfonic acid to yield the target compound. The preparation process of this invention uses a readily available chiral isomer as the raw material, avoiding the two chiral column separations required in existing methods, thus offering better economic efficiency. Furthermore, the resolving agent L-DBTA is inexpensive and readily available, avoiding expensive reagents; the reaction is mild, the operation is safe, and the separation is highly secure; column chromatography purification is avoided, facilitating industrial production.

Provided is use of NK cells in treating vitiligo and psoriasis. Specifically, provided are use of NK cells and a cancer-targeted drug in the preparation of a drug for treating patients with primary liver cancer or hepatocellular carcinoma accompanied by psoriasis, and use of NK cells and rituximab in the preparation of a drug for treating patients with hepatic cyst accompanied by psoriasis.

The present invention provides a polypeptide having the formula: St-R1-S1-Q-S2-R2 wherein St is a stalk sequence which, when the polypeptide is expressed at the surface of a target cell, causes the R and Q epitopes to be projected from the cell surface; R1 and R2 are a Rituximab-binding epitopes each having the an amino acid sequence selected from the group consisting of SEQ ID No. 1, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 and 16 or a variant thereof which retains Rituximab-binding activity, S1 and S2 are optional spacer sequences, which may be the same or different; and Q is a QBEnd10-binding epitope having the amino acid sequence shown as SEQ ID No. 2 or a variant thereof which QBEnd10-binding activity. The invention also provides a nucleic acid sequence encoding such a polypeptide and uses thereof in adoptive cell transfer.

The invention discloses a culture method of umbilical cord mesenchymal stem cells for treating cognitive impairment, and belongs to the technical field of cell culture. The culture method specifically comprises the following steps: (1) preparing a special culture medium; (2) umbilical cord pretreatment; and (3) cell culture. The traditional Chinese medicine extract (astragaloside), the B cell depleting agent (rituximab and ibrutinib) and the metabolism regulator (eicosapentaenoic acid) are jointly applied to the UC-MSCs in-vitro culture process, the multiplication capacity, the anti-inflammatory characteristic and the neural restoration function of the UC-MSCs can be synergistically enhanced, and therefore the cognitive disorder treatment efficiency of the UC-MSCs is remarkably improved.

The invention discloses a targeted immunomodulatory fusion protein for treating systemic lupus erythematosus, an engineered stem cell preparation for expressing the fusion protein as well as a preparation method and application of the engineered stem cell preparation. The fusion protein is composed of an anti-human CD20 single-chain antibody, an enhanced human IL-10 variant and a flexible connecting peptide, the complete amino acid sequence is SEQ ID NO5, the affinity to CD20 is basically equivalent to or better than that of rituximab, and the IL-10 activity is 1.8 times that of a wild type. The engineered stem cell preparation is obtained by transfecting human umbilical cord mesenchymal stem cells through lentivirus and screening puromycin, and the preparation can stably secrete fusion protein and is specifically combined with CD20 positive B cells. In-vitro experiments prove that B cell proliferation and IgG secretion can be remarkably inhibited, the urine protein positive rate and the dsDNA IgG level can be reduced in an in-vivo MRL / lpr mouse model, kidney pathological injuries are relieved, and the survival rate is increased. Precise treatment is achieved through a synergistic mechanism of targeted enrichment and local high-activity IL-10 delivery, the side effect of systemic immunosuppression is avoided, and the clinical transformation value is high.

The present invention provides the use of all-trans retinoic acid (ATRA) combined with low-dose rituximab in the preparation of a medicament for treating steroid-resistant or recurrent ITP. The dosage of rituximab is 100 mg weekly; the dosage of ATRA is 20 mg per square meter of body surface area per day. A multicenter randomized controlled trial demonstrated that the combination of ATRA and LD-RTX demonstrated superior efficacy and safety compared to LD-RTX alone in the treatment of patients with steroid-resistant or recurrent ITP.

The present invention relates to a hybridoma cell line and an antibody for detecting rituximab and its biosimilars, and their applications, belonging to the technical field of biological detection. The hybridoma cell line provided by the present invention is a combination of hybridoma cell lines, including hybridoma cell line RTX-9C02 and hybridoma cell line RTX-5B12, both of which can secrete monoclonal antibodies that specifically bind to rituximab. The produced monoclonal antibodies, RTX-9C02 antibody and RTX-5B12 antibody, can be jointly used to detect the blood drug concentration of rituximab and its biosimilars, achieving the effect of stably, accurately and highly specifically detecting rituximab and its biosimilars.

Provided are methods for inducing apoptosis of cells. The cells may be cancer cells (e.g., lymphoma cells). The cancer cells may be resistant to other known therapies, such as, for example, therapy with rituximab, a chimeric anti-CD20 monoclonal antibody. A method can include contacting the cells with a compound having the following structure: (MMRi36).